caa a22 4500 445312661 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0569-4 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0569-4 Cationic Liposomal Co-delivery of Small Interfering RNA and a MEK Inhibitor for Enhanced Anticancer Efficacy [Elektronische Daten] [Seung Kang, Hee-Jeong Cho, Gayong Shim, Sangbin Lee, Su-Hyeon Kim, Han-Gon Choi, Chan-Wha Kim, Yu-Kyoung Oh] Purpose: To test whether co-delivery of anticancer small interfering RNA (siRNA) and a chemical MEK inhibitor using cationic liposomes enhances anticancer activity in vitro and in vivo. Method: MEK inhibitor PD0325901 was encapsulated in lipid layers of N',N''-dioleylglutamide-based cationic liposomes (DGL). Mcl1-specific siRNA (siMcl1) was complexed to DGL or PD0325901-loaded liposomes (PDGL). Efficiency of cellular siRNA delivery was tested using fluorescent double-stranded RNA. Silencing of target proteins was evaluated using Western blotting and real-time quantitative polymerase chain reactions. In vivo anticancer activity was tested using xenografted mice. Results: Size and zeta potential of PDGL were similar to DGL. PDGL could deliver double-stranded RNA into cells with efficiencies comparable to DGL. Cellular co-delivery of siMcl1 and PD0325901 reduced expression of Mcl1 and pERK1/2 proteins and more effectively reduced tumor cell survival than other treatments. In mice, siMcl1 and PD0325901 co-delivered by PDGL inhibited growth of tumors 79%. Substantial apoptosis of tumor cells was observed following PDGL-mediated co-delivery of siMcl1, but not in other groups. Conclusions: PDGL-mediated co-delivery of siMcl1 and MEK inhibitor, PD0325901, could serve as a potential strategy for combination chemogene anticancer therapy. Springer Science+Business Media, LLC, 2011 co-delivery nationallicence combination therapy nationallicence liposome nationallicence MEK inhibitor nationallicence siRNA nationallicence DG : N',N”-dioleylglutamide nationallicence DGL : DG-based cationic liposomes nationallicence DOPE : dioleyl-sn-glycero-3-phosphoethanolamine nationallicence dsRNA : double-stranded RNA nationallicence ERK : extracellular signal-related kinase nationallicence GAPDH : glyceraldehyde-3-phosphate dehydrogenase nationallicence L2K : Lipofectamine 2000 nationallicence Mcl1 : myeloid cell leukemia sequence 1 nationallicence MEK : mitogen-activated protein/extracellular signal-regulated kinase kinase nationallicence MTT : 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide nationallicence PCR : polymerase chain reaction nationallicence PDGL : PD0325901-loaded cationic liposomes nationallicence pERK1/2 : phospho-ERK1/2 nationallicence siGL2 : luciferase-specific siRNA nationallicence siMcl1 : Mcl1-specific siRNA nationallicence siRNA : small interfering RNA nationallicence Kang Seung School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut Cho Hee-Jeong College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Daehak-dong, Gwanank-gu, 151-742, Seoul, South Korea aut Shim Gayong School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut Lee Sangbin School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut Kim Su-Hyeon School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut Choi Han-Gon College of Pharmacy, Hanyang University, 426-791, Ansan, South Korea aut Kim Chan-Wha School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut Oh Yu-Kyoung College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Daehak-dong, Gwanank-gu, 151-742, Seoul, South Korea aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3069-3078 0724-8741 28:12<3069 2011 28 11095 https://doi.org/10.1007/s11095-011-0569-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0569-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kang Seung School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut NATIONALLICENCE 700 1- Cho Hee-Jeong College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Daehak-dong, Gwanank-gu, 151-742, Seoul, South Korea aut NATIONALLICENCE 700 1- Shim Gayong School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut NATIONALLICENCE 700 1- Lee Sangbin School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut NATIONALLICENCE 700 1- Kim Su-Hyeon School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut NATIONALLICENCE 700 1- Choi Han-Gon College of Pharmacy, Hanyang University, 426-791, Ansan, South Korea aut NATIONALLICENCE 700 1- Kim Chan-Wha School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, 136-713, Seoul, South Korea aut NATIONALLICENCE 700 1- Oh Yu-Kyoung College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Daehak-dong, Gwanank-gu, 151-742, Seoul, South Korea aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3069-3078 0724-8741 28:12<3069 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer